miR-620 promotes tumor radioresistance by targeting 15-hydroxyprostaglandin dehydrogenase (HPGD)

Huang, Xiaoyong; Taeb, Samira; Jahangiri, Sahar; Korpela, Elina; Cadonic, Ivan; Yu, Nancy; Krylov, Sergey N.; Fokas, Emmanouil; Boutros, Paul C.; Liu, Stanley K.

doi:10.18632/oncotarget.4210

Cited by 32 publications

(20 citation statements)

References 59 publications

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“…HPGD was initially characterized as a key enzyme responsible for biological inactivation of prostaglandins 25 and subsequently shown to be involved in a number of human malignancies 22 , 40 – 42 . miR-620 is reported to up-regulate PGE2 expression by directly targeting HPGD, contributing to tumor radiation resistance 43 . An earlier study by He et al demonstrated that miR-21 participates in tumorigenesis via targeting the HPGD/PGE2 signaling pathway 44 .…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways

Yao¹,

Xu²,

Zhao³

et al. 2018

Cell Death Dis

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While the application of early screening and HPV vaccines has reduced the incidence and mortality rates of cervical cancer, it remains the third most common carcinoma and fourth leading cause of cancer-associated death among women worldwide. The precise mechanisms underlying progression of cervical cancer are not fully understood at present. Here, we detected significant down-regulation of 15-hydroxyprostaglandin dehydrogenase (HPGD) in cervical cancer tissues. Overexpression of HPGD inhibited cervical cancer cell proliferation, migration and anchorage-independent growth to a significant extent. To clarify the mechanisms underlying HPGD down-regulation in cervical cancer, miRNA microarray, bioinformatics and luciferase reporter analyses were performed. HPGD was identified as a direct target of miR-146b-3p displaying up-regulation in cervical cancer tissues. Similar to the effects of HPGD overexpression, down-regulation of miR-146b-3p strongly suppressed proliferation, migration and anchorage-independent growth of cervical cancer cells. Furthermore, HPGD negatively regulated activities of STAT3 and AKT that promote cervical cancer cell proliferation. Notably, HPV oncogenes E6 and E7 were determined as potential contributory factors to these alterations. Our results collectively suggest that the HPGD/miR-146b-3p axis plays a significant role in cervical cancer and may serve as a potentially effective therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways

Yao¹,

Xu²,

Zhao³

et al. 2018

Cell Death Dis

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“…miRNA are involved in all cell processes and have been of particular interest due to their role in cancer. They have been implicated in cell cycle progression, metastatic progression, and treatment response (Huang et al ., , ; Mesci et al ., ). Individual miRNA can regulate thousands of cellular pathways simultaneously (Huntzinger and Izaurralde, ).…”

Section: Introductionmentioning

confidence: 99%

“…Transcript degradation is the major outcome of miRNA-mRNA binding, occurring through the 5 0 -to-3 0 mRNA decay pathway (Huntzinger and Izaurralde, 2011). miRNA are involved in all cell processes and have been of particular interest due to their role in cancer. They have been implicated in cell cycle progression, metastatic progression, and treatment response (Huang et al, 2013(Huang et al, , 2015Mesci et al, 2017). Individual miRNA can regulate thousands of cellular pathways simultaneously (Huntzinger and Izaurralde, 2011).…”

Section: Introductionmentioning

confidence: 99%

miRNA‐106a and prostate cancer radioresistance: a novel role for LITAF in ATM regulation

et al. 2018

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Recurrence of high‐grade prostate cancer after radiotherapy is a significant clinical problem, resulting in increased morbidity and reduced patient survival. The molecular mechanisms of radiation resistance are being elucidated through the study of microRNA (miR) that negatively regulate gene expression. We performed bioinformatics analyses of The Cancer Genome Atlas (TCGA) dataset to evaluate the association between miR‐106a and its putative target lipopolysaccharide‐induced TNF‐α factor (LITAF) in prostate cancer. We characterized the function of miR‐106a through in vitro and in vivo experiments and employed transcriptomic analysis, western blotting, and 3′UTR luciferase assays to establish LITAF as a bona fide target of miR‐106a. Using our well‐characterized radiation‐resistant cell lines, we identified that miR‐106a was overexpressed in radiation‐resistant cells compared to parental cells. In the TCGA, miR‐106a was significantly elevated in high‐grade human prostate tumors relative to intermediate‐ and low‐grade specimens. An inverse correlation was seen with its target, LITAF. Furthermore, high miR‐106a and low LITAF expression predict for biochemical recurrence at 5 years after radical prostatectomy. miR‐106a overexpression conferred radioresistance by increasing proliferation and reducing senescence, and this was phenocopied by knockdown of LITAF. For the first time, we describe a role for miRNA in upregulating ATM expression. LITAF, not previously attributed to radiation response, mediates this interaction. This route of cancer radioresistance can be overcome using the specific ATM kinase inhibitor, KU‐55933. Our research provides the first report of miR‐106a and LITAF in prostate cancer radiation resistance and high‐grade disease, and presents a viable therapeutic strategy that may ultimately improve patient outcomes.

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“…It has been found that miR‐620 was overexpressed in human lung adenocarcinoma and regulated proliferation, invasion and migration of adenocarcinoma cells via targeting the tumor suppressor gene Glypican 5 24 . Another study in different types of cancer cells showed that the excessive expression of miR‐620 induced cell proliferation, deregulated G2/M checkpoint in vitro, and enhanced radiation resistance in vivo 25 . Here, we reported for the first time that miR‐620 knockdown suppressed TGF‐β1‐induced proliferation and increased apoptosis in ASMCs.…”

Section: Discussionmentioning

confidence: 99%

MiRNA‐620 promotes TGF‐β1‐induced proliferation of airway smooth muscle cell through controlling PTEN/AKT signaling pathway

Chen

Guo

Zhang

et al. 2020

The Kaohsiung J of Med Scie

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Asthma is an inflammatory syndrome characterized by airway hyperresponsiveness, bronchial inflammation, and airway remodeling. The hypertrophy and hyperplasia of airway smooth muscle cells (ASMCs) are hallmarks of bronchial remodeling in asthma. In this study, the regulatory effects of microRNA‐620 (miR‐620) on ASMC proliferation and apoptosis in response to transforming growth factor β1 (TGF‐β1) stimulation was investigated. The expression of miR‐620 was significantly upregulated in TGF‐β1‐treated ASMCs compared with vehicle‐treated cells. Downregulation of miR‐620 suppressed the proliferation and increased apoptosis in TGF‐β1‐stimulated ASMCs. Phosphatase and tensin homolog (PTEN) was predicted and confirmed as a downstream target of miR‐620. PTEN was upregulated in miR‐620‐inhibitor transfected ASMCs, but decreased in cells delivered with miR‐620 mimics. Moreover, knocking down miR‐620 alone efficiently reduced the phosphorylation of protein kinase B (AKT), decreased TGF‐β1‐induced proliferation and promoted apoptosis in ASMCs, whereas downregulation of PTEN in miR‐620 inhibitor‐transfected cells restored the activation of AKT, increased TGF‐β1‐triggered proliferation, and partially inhibited ASMC apoptosis. Taken together, the present study provided evidence that miR‐620 increased TGF‐β1‐mediated proliferation and suppressed apoptosis in ASMCs via the regulation of PTEN and AKT expression. These findings suggest that miR‐620/PTEN/AKT axis may be considered as a therapeutic target for asthma treatment.

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miR-620 promotes tumor radioresistance by targeting 15-hydroxyprostaglandin dehydrogenase (HPGD)

Cited by 32 publications

References 59 publications

Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways

Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways

miRNA‐106a and prostate cancer radioresistance: a novel role for LITAF in ATM regulation

MiRNA‐620 promotes TGF‐β1‐induced proliferation of airway smooth muscle cell through controlling PTEN/AKT signaling pathway

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